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Heparin Binding Protein in Early Differential Diagnosis of Bacterial Meningitis


Heparin-binding protein is a serine protease that is mobilized rapidly from emigrating polymorphonuclear leukocytes that acts as a chemoattractant activator of monocyte and macrophages. We investigated the potential role and efficacy of serum and cerebrospinal fluid heparin binding protein in differentiating bacterial meningitis from tuberculosis and viral meningitis. A case diagnosed with acute bacterial meningitis (n:37), viral meningitis (n:30) and tuberculous meningitis (n:30) was included in this study. The diagnosis was based on history, clinical criteria, cerebrospinal fluid examination, latex agglutination and culture, and response to therapy. Heparin-binding protein was measured using enzyme-linked immunosorbent technique in both cerebrospinal fluid and serum. Cerebrospinal fluid heparin-binding protein levels were 7.81 ± 0.23 ng/mL in bacterial meningitis, 6.11 ± 0.3 ng/mL in tuberculosis meningitis and 5.75 ± 0.1 ng/mL in viral meningitis. The mean serum level was 14.98 ± 1.1 ng/mL in bacterial meningitis, 6.89 ± 0.4 ng/mL in tuberculosis meningitis, and 6.02 ± 0.4 ng/mL in viral meningitis. Both heparin-binding protein levels were significantly higher in patients with bacterial meningitis. We found that serum and cerebrospinal fluid heparin binding protein is a useful marker for differentiating bacterial meningitis from non-bacterial meningitis.

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  1. Kandil M, Khalil G, El-Attar E, Shehata G, Hassan S. Accuracy of heparin binding protein: as a new marker in prediction of acute bacterial meningitis. Braz J Microbiol. 2018;49(1):213–9.

    CAS  Article  Google Scholar 

  2. Scheld WM, Whitley RJ, Marra MC. Infections of the central nervous system. 4th ed. Philadelphia: Wolters Kluwer Health, United States; 2014.

    Google Scholar 

  3. Linder A, Åkesson P, Brink M. Heparin-binding protein: diagnostic marker of acute bacterial meningitis. Crit Care Med. 2011;39:812–7.

    CAS  Article  Google Scholar 

  4. Carbonnelle E. Laboratory diagnosis of bacterial meningitis: usefulness of various tests for the determination of the etiological agent. Med Mal Infect. 2009;39(7–8):581–605.

    CAS  Article  Google Scholar 

  5. Bartt R. Acute bacterial and viral meningitis. Continuum Minneap Minn. 2012;18(6):1255–70.

    PubMed  Google Scholar 

  6. Soehnlein O, Lindbom L. Neutrophil-derived azurocidin alarms the immune system. J Leukoc Biol. 2009;85(3):344–51.

    CAS  Article  Google Scholar 

  7. Yang Y, Liu G, He Q, Shen J, Xu L, Zhu P, et al. A promising candidate: heparin-binding protein steps onto the stage of sepsis prediction. J Immunol Res. 2019;16:1–11.

    Google Scholar 

  8. Linder A, Soehnlein O, Åkesson P. Roles of heparin-binding protein in bacterial infections. J Innate Immunol. 2010;2:431–8.

    CAS  Article  Google Scholar 

  9. Linder A, Arnold R, Boyd JH, Zindovic M, Zindovic I, Lange A, et al. Heparin-binding protein measurement improves the prediction of severe infection with organ dysfunction in the emergency department. Crit Care Med. 2015;43(11):2378–86.

    CAS  Article  Google Scholar 

  10. Kjölvmark C, Påhlman LI, Åkesson P, Linder A. Heparin-binding protein (HBP)—a diagnostic biomarker of urinary tract infection in adults. Open Forum Infect Dis. 2014;23:4–10.

    Google Scholar 

  11. Llewelyn MJ, Berger M, Gregory M, Ramaiah R, Taylor AL, Curdt I. Sepsis biomarkers in unselected patients on admission to intensive or high-dependency care. Crit Care. 2013;17:60–5.

    Article  Google Scholar 

  12. Mariscalco MM. Heparin-binding protein: another neutrophil granule protein. another new biomarker? Crit Care Med. 2011;39(4):910–1.

    Article  Google Scholar 

  13. Kim J, Kim SE, Park BS, Shin KJ, Ha SY, Park J, et al. Procalcitonin as diagnostic and prognostic factor for tuberculosis meningitis. J Clin Neurol. 2016;12(3):332–9.

    Article  Google Scholar 

  14. Ozen M, Kanra G, Kara A, Secmeer G, Cengiz AB. Long-term beneficial effects of dexamethasone on intellectual and neuropsychological outcome of children with pneumococcal meningitis. Scand J Infec Dis. 2006;38(2):104–9.

    CAS  Article  Google Scholar 

  15. Ulutan F. Acute bacterial meningitis. Turkiye Klinikleri J Int Med Sci. 2006;2(28):69–74.

    Google Scholar 

  16. Fisher J, Linder A. Heparin-binding protein: a key player in the pathophysiology of organ dysfunction in sepsis. J Int Med. 2017;281(6):562–74.

    CAS  Article  Google Scholar 

  17. Linder A, Åkesson P, Inghamma M, Treutiger CJ, Linnér A, Sundén-Cullberg J. Elevated plasma levels of heparin-binding protein in intensive care unit patients with severe sepsis and septic shock. Crit Care. 2012;16:90–6.

    Article  Google Scholar 

  18. Holub M, Beran M. Should heparin-binding protein levels be routinely monitored in patients with severe sepsis and septic shock? Crit Care. 2012;16:133–8.

    Article  Google Scholar 

  19. Bentzer P, Fisher J, Kong HJ, Mörgelin M, Boyd JH, Walley KR, et al. Heparin-binding protein is important for vascular leak in sepsis. Intensive Care Med Exp. 2016;4(1):33–49.

    Article  Google Scholar 

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This study was financially supported by the Scientific Research Projects Governing Unit of Gaziantep University (Protocol number: SBF.17.03).

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ESN, MN, IK—research concept and design; ESN, MN, EE—collection and/or assembly of data; ESN, MN, EE—data analysis and interpretation; ESN, MN—writing the article; ESN, MN, IK—critical revision of the article; ESN, MN—final approval of article.

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Correspondence to Emine Siber Namiduru.

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Namiduru, E.S., Namiduru, M., Karaoğlan, İ. et al. Heparin Binding Protein in Early Differential Diagnosis of Bacterial Meningitis. Ind J Clin Biochem (2022).

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  • Heparin binding protein
  • Bacterial meningitis
  • Viral meningitis
  • Tuberculosis meningitis